The AZFc deletions are the most common type and depending on the missing genes, they could result into impaired spermatogenesis [24]. The genes in this locus are organized in a palindromic sequence, DAZ1/2 and DAZ3/4. The high prevalence of deletions occurring in AZFc could be explained by its specific structure, which could lead to intrachromosomal aberrations during nonallelic homologous recombination and high percentage of deletions of genes, located in the AZFc locus [19].
According to several research groups, the gr/gr deletion is a potential risk factor for a low number of sperm cells, found in the ejaculate [6, 7, 13]. However, there are also studies which deny its role and find no correlation between the deletion and impaired spermatogenesis [5, 25].
Despite the studies carried over the last couple of years in different populations, the impact of the gr/gr deletion on the spermatogenesis remains uncertain. As a result of this, testing for this marker is not recommended in the last guideline of the European Academy of Urology [11].
The findings from our study are in agreement with similar experiments from other countries, where there was no statistical difference in the distribution of gr/gr deletion among case and control subjects [2, 8, 21]. It is also suggested that no matter the lack of expression for sY1291 and the presence of gr/gr deletion, all copies of the DAZ gene are present. This could be due to a duplication of these genes, which occurred after the deletion as a compensatory mechanism [14]. It is a possible explanation of the fact that gr/gr deletions can be found in fertile patients with normozoospermia [22].
Our data showed no aggravating effect of the presence of gr/gr deletion on the impaired spermatogenesis after comparing patients with azoospermia and oligozoospermia. However, more patients with azoospermia should be included in order to further prove this finding.
Two of our case subject tested negative for both sY1291 and sY1191 markers and were later diagnosed with a complete deletion of the AZFc region. It could be suggested that only one missing marker is not specific enough for a deletion of the Y chromosome and only when both are absent this could result in an impaired spermatogenesis due to Y microdeletion.
Nevertheless, our results are in contradiction to the conclusions from two meta-analyses [4, 20]. The reason for this could be differences between the included case and control patients or due to different ethnic background since the Y chromosomal haplogroup could play a role in the frequency of gr/gr deletion. This deletion could be a polymorphic variant and because of the controversial results from different studies is not recommended to include it in the test panel for Y microdeletions [11].
One possible limitation of the study is the small number of included patients. Despite of that, there is a strong tendency towards nonstatistical significance since the p value is close to 1.00. That is why regardless of the small number of participants, the study is not underpowered.
Moreover, the prevalence and clinical effect of the deletion may depend on the Y chromosome background since the gr/gr deletion is a common finding among D2b, Q3, and Q1 Y haplogroups found in Asia. In men from Japan and China, who carry this mutation, there was no impaired spermatogenesis and it was present even in normoozoospermic men [18, 25].
However, in Bulgaria, different Y haplogroups are found. Around 40% of them belong to haplogroups E and I, 20% to R, and another 20% to J and G haplogroups. The rest 20% are divided among other haplogroups, which occur at a very low frequency [9]. There is data suggesting that partial deletions of the Y chromosome are a common finding in men from E haplogroups [3, 15], but we did not test our patients for their Y chromosomal background. It is unknown whether the Y haplogroups, found in Bulgaria, predispose to deletions and could explain the high prevalence of the gr/gr deletion in our study.